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Biomedical subjects

J Feldman

Publications and source records attributed to J Feldman.

At least 19 recordsLinked to original sources
PubMed2004

Aberrant auditory processing and atypical planum temporale in developmental stuttering.

OBJECTIVE: To learn if people with persistent developmental stuttering and atypical anatomy of their auditory temporal cortex have, when compared to control subjects, changes in fluency induced with delayed auditory feedback (DAF). BACKGROUND: DAF improves fluency in many individuals who stutter, and induces dysfluency in some normal people. The planum temporale (PT), a portion of auditory temporal cortex, is anatomically atypical in some adults who stutter and atypical anatomy might induce aberrant function. Thus, the people who demonstrate the paradoxical response to DAF might be those who have atypical anatomy. METHODS: Experimental subjects were adults with developmental stuttering (n = 14) and control subjects (n = 14) matched for age, sex, education, and handedness. Volumetric MRI scans of all subjects were obtained and the PT was measured in the right and left hemispheres. Based on these scans, subjects were classified as typical (leftward PT asymmetry) or atypical (rightward PT asymmetry). Prose passages were read at baseline, with non-altered feedback (NAF), and with DAF, and fluency was measured in these three conditions. RESULTS: At baseline the adults with developmental stuttering were significantly more dysfluent than controls (p < 0.0005). Controls' fluency did not significantly change with DAF, but DAF improved fluency in adults with developmental stuttering (p < 0.0005). In the stutter group enhanced fluency was associated with atypical (rightward) PT asymmetry, and the presence of typical (leftward) PT asymmetry was not associated with any significant change in fluency. The individuals with atypical PT asymmetry also had more severe stuttering at baseline compared to the experimental subjects with typical PT anatomy. CONCLUSIONS: In adults with persistent developmental stuttering and atypical PT anatomy, fluency is improved with DAF. These experimental subjects who showed improvement had more severe stuttering at baseline. Anomalous PT anatomy may be a neural risk for developmental stuttering in some individuals. Although a number of explanations are tenable, it may be that atypical rightward PT asymmetry may alter speech feedback, and treatment with DAF might allow these people to compensate.

Adult↗
PubMed2003

Incident hepatitis C virus in women with human immunodeficiency virus infection.

Individuals infected with human immunodeficiency virus type 1 (HIV-1) are frequently coinfected with hepatitis C virus (HCV). Acute HCV infection is often asymptomatic and poorly understood. We conducted a historical prospective study of HCV antibody and viremia in plasma samples obtained during 1994-1999 from a cohort of initially HIV-1-infected, HCV-uninfected women and from HIV-1-HCV-uninfected women. Twenty-two (1.5%) of 1517 experienced seroconversion. Of these, 14 (64%) truly acquired a new infection as assessed by enzyme immunoassay response and new-onset viremia. The incidence rate in HIV-1-infected women was 2.7 cases per 1000 person-years; it was 3.3 cases per 1000 person-years in HIV-1-seronegative women (relative risk, 1.21; P=.75). Acquisition of HCV was associated with any history of drug use (P<.01). Five of 12 viremic, seroconverting individuals cleared viremia. Incident HCV infection among HIV-1-infected and HIV-1-uninfected women was low. It was linked to drug use and commonly resolved.

Adult↗
PubMed2003

I(1) imidazoline receptors involved in cardiovascular regulation: where are we and where are we going?

Clonidine-like drugs (hybrid drugs) reduce blood pressure by acting centrally at both alpha(2)-adrenergic receptors (alpha(2)AR) and I(1) receptors (I(1)R). Some attempts at cloning I(1)R have failed, probably because of the lack of selectivity of the ligands. Recently, compounds acting exclusively at I(1)R were synthesized: LNP 911, LNP509, and S23515. For example, LNP911 has a K(d) value of 1.7 nmol/L at I(1)R. LNP509 and S23515 reduce blood pressure when injected centrally in anesthetized animals, whereas S23757 behaves as an antagonist of hypotensive imidazolines. LNP509 reduces blood pressure even in genetically engineered mice lacking functional alpha(2)AR. An exclusive action at central I(1)R is therefore sufficient to modify blood pressure. With the help of drugs selective for I(1)R and alpha-methylnoradrenaline, selective for alpha(2)AR, we showed that imidazoline and alpha(2)-adrenergic mechanisms interact synergistically in controlling the blood pressure. Such a synergism may explain the very powerful hypotensive effects of hybrid drugs. The new ligands selective for I(1)R will be very helpful to investigate the molecular features and the signaling system of I(1)R.

Animals↗
PubMed2003

Protective effects of centrally acting sympathomodulatory drugs on myocardial ischemia induced by sympathetic overactivity in rabbits.

It is recognized that an imbalance of the autonomic nervous system is involved in the genesis of ventricular arrhythmia and sudden death during myocardial ischemia. In the present study we investigated the effects of clonidine and rilmenidine, two centrally acting sympathomodulatory drugs, on an experimental model of centrally induced sympathetic hyperactivity in pentobarbital-anesthetized New Zealand albino rabbits of either sex (2-3 kg, N = 89). We also compared the effects of clonidine and rilmenidine with those of propranolol, a beta-blocker, known to induce protective cardiovascular effects in patients with ischemic heart disease. Central sympathetic stimulation was achieved by intracerebroventricular injection of the excitatory amino acid L-glutamate (10 micro mol), associated with inhibition of nitric oxide synthesis with L-NAME (40 mg/kg, iv). Glutamate triggered ventricular arrhythmia and persistent ST-segment shifts in the ECG, indicating myocardial ischemia. The intracisternal administration of clonidine (1 microg/kg) and rilmenidine (30 microg/kg) or of a nonhypotensive dose of rilmenidine (3 microg/kg) decreased the incidence of myocardial ischemia (25, 14 and 25%, respectively, versus 60% in controls) and reduced the mortality rate from 40% to 0.0, 0.0 and 12%, respectively. The total number of ventricular premature beats per minute fell from 30 +/- 9 in the control group to 7 +/- 3, 6 +/- 3 and 2 +/- 2, respectively. Intravenous administration of clonidine (10 micro g/kg), rilmenidine (300 microg/kg) or propranolol (500 microg/kg) elicited similar protective effects. We conclude that clonidine and rilmenidine present cardioprotective effects of central origin, which can be reproduced by propranolol, a lipophilic beta-blocking agent.

Adrenergic beta-Antagonists↗
PubMed2001

Synthesis and biological evaluation of pyrrolinic isosteres of rilmenidine. Discovery of cis-/trans-dicyclopropylmethyl-(4,5-dimethyl-4,5-dihydro-3H-pyrrol-2-yl)-amine (LNP 509), an I1 imidazoline receptor selective ligand with hypotensive activity.

To find new compounds selective for purported I1 imidazoline receptors (I1Rs) over I2 imidazoline binding sites (I2BS) and alpha2-adrenoceptors (alpha2ARs), a series of pyrrolinic isosteres of rilmenidine has been prepared and their biological activity at I1Rs, I2BS, and alpha2ARs evaluated. This isosteric replacement provided us with compounds which still bound to I1Rs but not to I2BS nor to alpha2ARs. A limited structure-affinity relationship was generated around the heterocyclic moiety of these ligands. One compound in this series, LNP 509 (1e) [cis-/trans-dicyclopropylmethyl-(4,5-dimethyl-4,5-dihydro-3H-pyrrol-2-yl)-amine], had no detectable affinity at alpha2ARs yet was capable of lowering blood pressure after central administration. These pyrrolinic analogues constitute a new chemical class of imidazoline related compounds with high selectivity for the I1Rs. They could be used as new tools in the study of I1Rs and in the conception of new centrally acting hypotensive drugs.

Adrenal Medulla↗
PubMed2001

What is a visual object? Evidence from target merging in multiple object tracking.

The notion that visual attention can operate over visual objects in addition to spatial locations has recently received much empirical support, but there has been relatively little empirical consideration of what can count as an 'object' in the first place. We have investigated this question in the context of the multiple object tracking paradigm, in which subjects must track a number of independently and unpredictably moving identical items in a field of identical distractors. What types of feature clusters can be tracked in this manner? In other words, what counts as an 'object' in this task? We investigated this question with a technique we call target merging: we alter tracking displays so that distinct target and distractor locations appear perceptually to be parts of the same object by merging pairs of items (one target with one distractor) in various ways - for example, by connecting item locations with a simple line segment, by drawing the convex hull of the two items, and so forth. The data show that target merging makes the tracking task far more difficult to varying degrees depending on exactly how the items are merged. The effect is perceptually salient, involving in some conditions a total destruction of subjects' capacity to track multiple items. These studies provide strong evidence for the object-based nature of tracking, confirming that in some contexts attention must be allocated to objects rather than arbitrary collections of features. In addition, the results begin to reveal the types of spatially organized scene components that can be independently attended as a function of properties such as connectedness, part structure, and other types of perceptual grouping.

Analysis of Variance↗
PubMed2001

Respective contributions of alpha-adrenergic and non-adrenergic mechanisms in the hypotensive effect of imidazoline-like drugs.

The hypotensive effect of imidazoline-like drugs, such as clonidine, was first attributed to the exclusive stimulation of central alpha2-adrenoceptors (alpha2ARs). However, a body of evidence suggests that non-adrenergic mechanisms may also account for this hypotension. This work aims (i) to check whether imidazoline-like drugs with no alpha2-adrenergic agonist activity may alter blood pressure (BP) and (ii) to seek a possible interaction between such a drug and an alpha2ARs agonist alpha-methylnoradrenaline (alpha-MNA). We selected S23515 and S23757, two imidazoline-like drugs with negligible affinities and activities at alpha2ARs but with high affinities for non-adrenergic imidazoline binding sites (IBS). S23515 decreased BP dose-dependently (-27+/-5% maximal effect) when administered intracisternally (i.c.) to anaesthetized rabbits. The hypotension induced by S23515 (100 microg kg(-1) i.c.) was prevented by S23757 (1 mg kg(-1) i.c.) and efaroxan (10 microg kg(-1) i.c.), while these compounds, devoid of haemodynamic action by themselves, did not alter the hypotensive effect of alpha-MNA (3 and 30 microg kg(-1) i.c.). Moreover, the alpha2ARs antagonist rauwolscine (3 microg kg(-1) i.c.) did not prevent the effect of S23515. Finally, whilst 3 microg kg(-1) of S23515 or 0.5 microg kg(-1) of alpha-MNA had weak hypotensive effects, the sequential i.c. administration of these two drugs induced a marked hypotension (-23+/-2%). These results indicate that an imidazoline-like drug with no alpha2-adrenergic properties lowers BP and interacts synergistically with an alpha(ARs agonist.

Animals↗
PubMed2001

Does it make sense to develop new centrally acting cardiovascular drugs?

1. The autonomic nervous system plays a pivotal role in modulating all the components of the cardiovascular regulation. Therefore, one can assume that drugs targeting this system may be useful in the management of several cardiovascular diseases. 2. Drugs acting on central nervous system centres seem to be modulators rather than blockers; as such, they are expected to preserve the contraregulatory processes and to generate only a few side effects. 3. Because the sympathetic nervous system is largely involved in the regulation of vasomotor tone, centrally acting antihypertensive drugs were developed first. 4. Recently, new leader compounds selective for non- adrenergic imidazoline recepetors have been synthetized. Although such drugs have no capacity to activate alpha2-adrenoceptors, they have been proven to be hypotensive. These drugs are expected to be even better tolerated than the currently available centrally active drugs. They may also have additional beneficial effects. 5. Here, the experimental evidence suggesting that such drugs may be useful in the management of some cardiac arrhythmias and/or left ventricular dysfunction will be reviewed.

Animals↗
PubMed2001

A case-control study of beliefs and behaviors associated with sexually transmitted disease occurrence in Estonia.

BACKGROUND: Epidemiologic data document rapidly increasing sexually transmitted disease (STD) rates throughout Eastern Europe. GOAL: This case-control study was designed to delineate factors contributing to the STD epidemic in Estonia. STUDY DESIGN: For this study, 189 study participants and 112 control subjects completed a behavioral questionnaire and underwent testing for Neisseria gonorrhoeae, Chlamydia trachomatis, and Treponema pallidum. RESULTS: The prevalence of STDs among the control subjects was 32%. Although the participants believed that condoms prevent STDs, only 17% reported consistent use. Methods believed to prevent transmission included washing the genitals (65%), urinating (26%), douching (35%), and using oral contraceptives (19%). An interaction between sex and travel outside Estonia (odds ratio, 0.1; 95% CI, 0-0.7) reflects the fact that males with STDs were more likely to report travel (46% of participants and 45.5% of control subjects with STD) than were those without STD (16.1% of controls without STD). CONCLUSIONS: STD rates are related to high-risk sexual behavior among males traveling outside of Estonia. Intervention is needed to promote understanding of disease transmission dynamics in this area, and to decrease sexual risk behavior, particularly in the context of travel.

Adolescent↗
PubMed2001

Nitric oxide and central antihypertensive drugs: one more difference between catecholamines and imidazolines.

NO is known to be involved in the peripheral and central regulation of the cardiovascular function. It plays a neuromodulatory role via a direct action on presynaptic nerve terminals, stimulating the release of gamma-aminobutyric acid, glutamate, and norepinephrine. Our aim was to study the possible role of NO in the cardiovascular effects of the central antihypertensive drugs clonidine, rilmenidine, and alpha-methyl-norepinephrine (alpha-MNA). Sites and mechanisms of the hypotensive action of these drugs were different; clonidine and rilmenidine acted on imidazoline receptors in the nucleus reticularis lateralis, whereas alpha-MNA acted upon alpha(2)-adrenoceptors in the nucleus tractus solitarius. The influence of N:(G)-nitro-L-arginine, an NO synthase inhibitor, on the central hypotensive effects of these drugs was investigated in pentobarbital-anesthetized rabbits. The intracisternal (IC) administration of alpha-MNA (30 microg/kg) induced hypotension (79+/-2 versus 103+/-4 mm Hg) and bradycardia (222+/-8 versus 278+/-4 bpm) (P:<0.05) (n=5). Clonidine (0.07 microg/kg IC) also induced hypotension (69+/-5 versus 99+/-4 mm Hg) and bradycardia (266+/-7 versus 306+/-10 bpm) (P:<0.05) (n=5). In addition to clonidine, rilmenidine (1 microg/kg IC) induced hypotension (64+/-4 versus 97+/-4 mm Hg) and bradycardia (264+/-11 versus 310+/-4 bpm) (P:<0.05) (n=5). Pretreatment with N:(G)-nitro-L-arginine (900 microg/kg IC) completely prevented the hypotensive effect of alpha-MNA but influenced the cardiovascular effects of neither clonidine nor rilmenidine. These results confirm that imidazoline drugs, such as clonidine, rilmenidine, and the catecholamine alpha(2)-adrenoceptor agonist alpha-MNA, have distinct mechanisms of action.

Animals↗
PubMed2001

Experience and covariates of depressive symptoms among a cohort of HIV infected women.

OBJECTIVES: The objectives of this study are to assess (a) the level of depressive symptoms among a cohort of HIV infected women and comparable controls and (b) the relationship with covariates including socioeconomic status, substance use, social relations, disease status. METHODS: Participants were enrolled in the Women's Interagency HIV Study (WIHS). Depressive symptoms were measured using the Center for Epidemiological Studies Depression Scale (CESD). Data from 1993 HIV seropositive and 551 seronegative women are presented. RESULTS: Of HIV positive women 57.7% of HIV positive women scored 16 or higher on the CESD (ns) as compared to 55.0% of HIV negative women; at a cutoff of 23, the percents were 40.4% and 35.9% respectively (p = .06). The mean score was high 19.8 but not significantly different between groups. Scores were higher among women who had less education, lower income, were of Hispanic ethnicity, used alcohol or drugs, experienced domestic abuse, had more than one partner, or had less supportive relationships. Among infected women, higher CESD scores were not significantly associated with CD4 cell count but were elevated for self-reported Class C AIDS defining clinical conditions. CONCLUSIONS: The scores on the CESD were elevated for both HIV positive and HIV negative women and the differences between the groups were small. Lower socioeconomic status and social support and higher substance use and domestic abuse were associated with depressive symptoms similarly for both groups.

Analysis of Variance↗
PubMed2001

Bayesian contour integration.

The process by which the human visual system parses an image into contours, surfaces, and objects--perceptual grouping--has proven difficult to capture in a rigorous and general theory. A natural candidate for such a theory is Bayesian probability theory, which provides optimal interpretations of data under conditions of uncertainty. But the fit of Bayesian theory to human grouping judgments has never been tested, in part because methods for expressing grouping hypotheses probabilistically have not been available. This paper presents such methods for the case of contour integration--that is, the aggregation of a sequence of visual items into a "virtual curve." Two experiments are reported in which human subjects were asked to group ambiguous configurations of dots (in Experiment 1, a sequence of five dots could be judged to contain a "corner" or not; in Experiment 2, an arrangement of six dots could be judged to fall into two disjoint contours or one smooth contour). The Bayesian theory accounts extremely well for subjects' judgments, explaining more than 75% of the variance in both tasks. The theory thus provides a far more quantitatively precise account of human contour integration than has been previously possible, allowing a very precise calculation of the subjective goodness of a virtual chain of dots. Because Bayesian theory is inferentially optimal, this finding suggests a "rational justification," and hence possibly an evolutionary rationale, for some of the rules of perceptual grouping.

Adult↗
PubMed2000

Minimization of Boolean complexity in human concept learning.

One of the unsolved problems in the field of human concept learning concerns the factors that determine the subjective difficulty of concepts: why are some concepts psychologically simple and easy to learn, while others seem difficult, complex or incoherent? This question was much studied in the 1960s but was never answered, and more recent characterizations of concepts as prototypes rather than logical rules leave it unsolved. Here I investigate this question in the domain of Boolean concepts (categories defined by logical rules). A series of experiments measured the subjective difficulty of a wide range of logical varieties of concepts (41 mathematically distinct types in six families--a far wider range than has been tested previously). The data reveal a surprisingly simple empirical 'law': the subjective difficulty of a concept is directly proportional to its Boolean complexity (the length of the shortest logically equivalent propositional formula)--that is, to its logical incompressibility.

Humans↗